Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

Early correction of childhood malocclusion is timely managing morphological, structural, and functional abnormalities at different dentomaxillofacial developmental stages. The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion. This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence, aiming to provide general guidance on appropriate imaging examination selection, comprehensive and accurate imaging assessment for early orthodontic treatment patients.
Humans ; Malocclusion/diagnostic imaging* ; Child ; Consensus

OBJECTIVE To provide a reference for the adjustment of antibacterial drug regimens， identification of adverse reactions， and personalized pharmaceutical care for patients with bullous pemphigoid and pulmonary aspergillosis combined with disseminated Nocardia farcinica infection. METHODS Clinical pharmacists participated in the entire treatment process of a patient with bullous pemphigoid and pulmonary aspergillosis combined with disseminated N. farcinica infection. Evidence-based medicine was used to assist in the selection of an initial combined drug regimen against nocardiosis， and timely communication with the microbiology laboratory to provide early antimicrobial susceptibility data. When the patient exhibited epilepsy， the suspected drugs were identified， and it was reminded that imipenem-cilastatin sodium could affect the efficacy of valproic acid. It was suggested to replace valproic acid with levetiracetam for anti-epileptic treatment and to discontinue imipenem-cilastatin sodium. During treatment， it was recommended to monitor the blood concentrations of voriconazole and linezolid， and assist in adjusting the dosage promptly based on the monitoring results. RESULTS The physicians accepted the recommendations of the clinical pharmacists. The patient’s condition improved， and they were discharged with medication. CONCLUSIONS Based on evidence-based medical evidence， antimicrobial susceptibility test results， and blood concentration monitoring data， clinical pharmacists assist clinicians in selecting a sensitive anti-infective regimen for the patient， identifying adverse reactions， adjusting the treatment regimen and providing full-course medication monitoring to ensure the safety and efficacy of clinical drug therapy.

AIM: To analyze the modeling characteristics and validation indexes of diabetic retinopathy model, analyze the shortcomings of the present animal experimental modeling, and provide a reference basis for the establishment of the standardization of the diabetic retinopathy model.METHODS: Literatures related to animal experiments on diabetic retinopathy were searched through the databases of CNKI, Wanfang, VIP and PubMed, and the experimental animal species, grade, gender, age, modeling method, modeling period, validation indexes, and other indexes were summarized and analyzed.RESULTS: The 275 papers that met the criteria were included. The animal models of diabetic retinopathy were mainly SD rats and Wistar rats, the sex of the experimental animals was mainly male, and the animal breeds were mostly of the SPF class. The age of most of the animals used was in the range of 6-8 weeks old; the modeling was based on those who established the type 1 diabetes model, mainly using STZ as the induction model. While the type 2 diabetes model was based on the high-fat, high-sugar diet combined with STZ. The modeling criteria were verified by detecting retinal morphology and structure, retinal vascularization, retinal function, and retinal cell apoptosis. In addition, the model was evaluated by detecting abnormal vascular proliferation, oxidative stress indicators, and inflammatory factor levels in retinal tissues, as well as abnormal vascular proliferation and inflammatory factor levels in aqueous humour, vitreous humor, and blood serum.CONCLUSION: Although the animal model of diabetic retinopathy has become a hotspot, the existing review is not comprehensive. Therefore, we summarized and analyzed the elements of the animal model through literature collation, including its characteristics and limitations, and providing methodological references for the establishment of the model, with a view to laying a solid foundation for the subsequent clinical and basic research of traditional Chinese medicine.

Purpose/Significance To put forward strategies for the open sharing of biomedical scientific data and provide theoretical support for the sustainable development of scientific data in China.Method/Process The paper adopts the multiple-case study method to analyze open sharing practices of four international typical biomedical scientific data platforms,including UK Biobank,National Center for Biotechnology Information(NCBI),Global Initiative on Sharing All Influenza Data(GISAID)and Cortellis Drug Discovery Intelli-gence(CDDI).Result/Conclusion Suggestions are proposed based on three processes of before,during and after data sharing.In the construction of data resources,the division of data rights and rights subjects should be determined.The open use of data should be differ-entiated according to data attributes.In terms of data ecology construction,mechanisms and measures to promote data value-added should be formulated.

Background and purpose:BRCA1/2 plays an important role in maintaining the genome stability.Whether BRCA1/2 germline mutation could increase the tumor sensitivity to radiotherapy,thereby inducing secondary primary cancer after radiotherapy is unclear.This study aimed to investigate whether postoperative radiotherapy is a risk factor for the development of second primary cancer in triple-negative breast cancer(TNBC)patients with BRCA1/2 germline mutation.Methods:This research was based on a previously reported retrospective cohort,i.e.,the Fudan University Shanghai Cancer Center TNBC cohort.Between January 1,2007 and December 31,2014,a total of 292 female TNBC patients with BRCA1/2 mutation were enrolled.We performed logistic regression analysis in patients without BRCA1/2 germline mutation(n=261)and BRCA1/2 germline mutation patients(n=31),respectively,to assess the risk factors affecting the incidence of second primary cancer.We then performed interactive analysis on the above two analyses to evaluate the interactive effect between BRCA1/2 germline mutation and postoperative radiotherapy.P<0.05 indicates a statistically significant difference.The research was approved by Fudan University Shanghai Cancer Center TNBC Ethics Committee(050432-4-2108),and each patient provided written informed consent.Results:Logistic regression analysis in patients with BRCA1/2 germline mutations showed that postoperative radiotherapy significantly increased the risk of secondary primary disease compared to non-radiotherapy[odds ratio(OR)=2.475,95%confidence interval(CI):1.933-3.167,P<0.001].In patients without BRCA1/2 germline mutation,the effect of radiotherapy on the incidence of second primary tumor was not significant.There was a significant interaction between BRCA1/2 germline mutation and postoperative radiotherapy for the incidence of secondary primary cancer(OR=9.710,95%CI:0.320-295.250,P=0.193).Conclusion:Although statistical analysis results show that patients with BRCA1/2 germline mutations have an increased risk of developing a second primary tumor after postoperative radiotherapy compared to patients who have not received radiotherapy,there is no significant correlation between BRCA1/2 germline mutations and radiotherapy for the development of a second primary tumor.Therefore,patients with BRCA1/2 germline mutations who receive radiotherapy after surgery may not increase the risk of developing a second primary tumor.

ObjectiveTo analyze the current situation and frontier trends of the research on intelligent rehabilitation in China. MethodsLiteratures with the theme of intelligent rehabilitation were retrieved from CNKI, Wanfang database and VIP database from 2014 to 2024, and visual analysis was carried out using CiteSpace 6.2.R4. ResultsA total of 1 861 Chinese literatures were included. The annual number of publications in the field of intelligent rehabilitation in China showed an upward trend, reaching the highest value of 659 in 2023. The institution that has published the largest number of Chinese literature is Shanghai University of Science and Technology. The high-frequency Chinese keywords included stroke, rehabilitation training, robot, etc., and the bursting keywords included early intervention, newborn, cerebral palsy, etc. ConclusionThe annual number of publications in the field of intelligent rehabilitation is on the rise. Artificial intelligence, stroke and intellectual development are the key research areas. In-depth research on the application of technologies such as artificial intelligence and robots in the field of rehabilitation and focusing on the rehabilitation needs of special populations may be the research trends in the future.

Objective To investigate the dietary intakes of postoperative patients with digestive malignant tumor during their recovery at home and explores the correlation of the intakes with the food nutritional knowledge of their primary family care-givers.Methods A total of 108 primary caregivers of prospective patients with digestive malignant tumors were selected for a sur-vey conducted at home from October 2022 to March 2023 in Guangzhou,from two tertiary hospitals.In this cross-sectional study,this paper investigated these caregivers using its general information questionnaire,a nutritional knowledge-attitude-behavior ques-tionnaire,and a simple dietary self-assessment tool(SDSAT).Results The SDSAT score of the patients was collected(4.16±1.22).Significant differences were observed among patients with various tumor types in terms of the recovery time at home after surgery.The total score of family primary caregivers'nutritional knowledge,attitude,and behavior was(47.64±6.97).Pearson's correlation analysis revealed a positive correlation between the knowledge of dietary guidelines and the patient's dietary intakes during home stay(r=0.285,P＜0.05).Multiple linear regression analysis revealed that caregivers'knowledge of dieta-ry guidelines significantly influenced the dietary intake of the prospective patients.Conclusion It is essential to regularly monitor the dietary intake of prospective patients at home.Medical personnel can concentrate on intervening with the patient's caregivers and encouraging them to participate in nutrition management together.This approach can improve the quality of family care and the nutritional status of the patients.

Objective To evaluate the detection performance of common strains and the antimicrobial binding capacity of four blood culture systems made by BMX-FA/N Plus,Zhengzhou Anto,Zhuhai DIER and Chongqing Zhongyuan.Methods According to the common pathogens of clinical bloodstream infections in Wuhan No.1 Hospital,ATCC standard isolates of Staphylococcus aureus,Streptococcus pneumoniae,Enterococcus faecalis,Escherichia coli,Pseudomonas aeruginosa,Haemophilus influenzae,Stenotrophomonas Maltophil,Bacteroides tenuis and Candida glabla were chosen to explore.Prefabricated bacterial suspension and sterile horse blood were injected into different brands of blood culture systems to simulate the blood samples of patients with non-antibiotic treatment and antibiotic treatment.Six commonly used clinical antibiotics,Imipenem,Piperacillin/Tazobactam,Cefoperazone/Sulbactam,Levofloxacin,Vancomycin and Micafungine,were added to the blood samples after simulated antibiotic treatment.The performance was evaluated by recording the positive bottles and the detection time of each brand culture systems within five days with and without antibiotic.Results In the absence of antibiotic,four blood culture systems showed 100％recovery on all of the pathogens.Staphylococcus aureus,Pseudomonas aeruginosa and Haemophilus influenzae were recovered earlier in DIER aerobic bottles than BMX-FA Plus aerobic bottles,and the differences were statistically significant(t=2.608,5.547,12.247,all P＜0.05).The time to detection of Staphylococcus aureus,Streptococcus pneumoniae,Enterococcus faecalis and Haemophilus influenzae in Zhongyuan anaerobic bottles was significantly faster than that of BMX-FA Plus anaerobic bottles,with an average shortening of 1.92～10.80 h,and the differences were statistically significant(t=30.187,5.367,33.068,24.855,all P＜0.05).When antibiotics added,BMX-FA Plus culture bottle showed 100％recovery to all the detecting pathogens with the peak concentration antibiotics except Cefoperazone/Sulbactam,while the recovery in Zhongyuan blood culture bottle also was 100％with peak concentration antibiotics of Piperacillin/Tazobactam,Levofloxacin and Micafunzin.The peak concentration of imipenem antibiotics in domestic bottles was only detected in Anto anaerobic bottles,with lower positive detection rate(66.7％)lower than that of BMX-FA Plus(100％)and a later detection,and the difference was statistically significant(t=-21.000,P=0.030).Conclusion In the absence of antibiotic interference,the positive detection rate of the above pathogens are the same for four blood culture systems,and the time to detection of DIER and Zhongyuan systems is shorter than that of BMX-FA/N Plus.In the presence of antibiotic interference,the detection ability to pathogens in BMX-FA/N Plus system is the best,followed by domestic Zhongyuan system.

Purpose/Significance To discuss the issues of scientific data ownership in the realm of health in China,so as to provide theoretical references for the policy formulation of open sharing and flow of scientific data.Method/Process By exploring data rights based on data types,the study preliminarily constructs a data rights system,proposes a data rights distribution model,and examines the rights transfer process from the perspective of the data value chain.Result/Conclusion A rights system centered on data property rights,personal rights and regulatory rights is established.An"inherent rights+transferable rights"data rights distribution model is proposed and it has been implemented within the data value chain.